Answer: C - Intraneural perineurioma

Sections show cross-sections of multiple nerve fascicles, each containing numerous variably sized whorled structure, composed of a concentric population of spindle cells and collagen fibers (so called "pseudo-onion bulb" structures). Immunostains show the ensheathing cells to be perineurial cells (positive for  EMA and negative for S-100), with Collagen IV highlighting surrounding basement membrane material. Within the structures, neurofilament highlights axons that are encircled by Schwann cells (S-100 positive). Electron microscopy confirmed the presence of myelinated axons within the pseudo-onion bulb structures, with overall extensive loss of myelinated axons across all fascicles. Altogether, these findings support a diagnosis of intraneural perineurioma. 

Intraneural perineuriomas are rare, benign intraneural neoplasms that typically result in fascicular or nodular enlargement of nerve fascicles. Histologically, they are composed of concentric proliferations of perineural cells that form "pseudoonion bulb structures" around nerve fibers. These are distinguished from "true onion bulbs", which are composed of Schwann cells interlaced with collagen fibers, which are typically seen in reactive and demyelinating conditions (e.g. localized hypertrophic neuropathy, Charcot- Marie Tooth disease). In contrast to Schwann cells, perineurial cells are negative for S-100, and express EMA, GLUT1 and Claudin-1. Within both pseudo-onion bulb and onion bulb structures, axonal elements can be seen. Schwannomas, on the other hand, are diffusely S-100 positive and displace axons to the periphery rather than harboring them within the lesion itself.  Finally, while neurofibromas may have onion-bulb structures and intraneural growth, these lesions are typically more heterogeneous in their morphology, often featuring collagen bundles, stromal mucin and degenerative atypia. Additionally, S-100 would highlight scattered Schwann cells throughout the tumor.  

Intraneural perineuriomas generally involve major nerves of young adults, whom typically present with motor disturbances. They are very slow growing lesions, but some may result in the eventual loss of sensorimotor function in the affected nerve. Treatment of these lesions is still controversial without a general consensus, and includes conservative (non-invasive) management . Surgical approaches (e.g. resection and nerve grafting) may offer benefit in some patients, and is most commonly recommended in patients with progressive neurological deficit and localizable single lesion. Of note, a recent paper demonstrated a subset of intraneural perineuriomas to have recurrent mutations in the TRAF gene, similar to that seen in some meningiomas. 

References

Klein CJ, Wu Y, Jentoft ME, et al. Genomic analysis reveals frequent TRAF7 mutations in intraneural perineuriomas. Ann Neurol. 2017;81(2):316-321. 

Mauermann ML, Amrami KK, Kuntz NL, et al. Longitudinal study of intraneural perineurioma--a benign, focal hypertrophic neuropathy of youth. Brain. 2009;132(Pt 8):2265-2276.

Uerschels A-K, Krogias C, Junker A, Sure U, Wrede KH, Gembruch O. Modern treatment of perineuriomas: a case-series and systematic review. BMC Neurol. 2020;20(1):55.